Core D: Neuropathology Care Abstract The Neuropathology (NP) Core fulfills several important roles within the University of Pittsburgh ADRC (PITT-ADRC). Postmortem neuropathological confirmation of the clinical diagnosis of Alzheimer's disease (AD) and related disorders and the assessment of co-existing neurodegenerative and vascular disease processes is essential to promote progress in diagnosis, treatment and prevention of AD. Since its inception, the NP Core has collected and characterized >600 brains from PITT-ADRC subjects at various disease stages. This resource has been extensively utilized for teaching purposes and for research studies by local and national investigators to develop amyloid imaging agents and correlate in vivo amyloid imaging results with postmortem findings, improve our understanding of genetic factors contributing to AD risk and advance our knowledge regarding the neurobiology of psychiatric comorbidities and neuroinflammatory processes. Our proposed approach to fulfill the diagnostic, tissue banking, research and educational roles of the NP Core is outlined in five specific aims: 1) The NP Core will continue to maintain and expand a well-catalogued bank of frozen and formalin-fixed tissue samples of ADRC subjects. A special emphasis will be placed on harvesting brains from cognitively normal and mildly impaired subjects, which represent a main recruitment focus of our Clinical Core. 2) All banked cases will undergo detailed diagnostic evaluation using the latest consensus criteria. Results will be shared with ADRC clinical staff, families and uploaded to centralized databases (NACC). 3) The NP core will increasingly take advantage of new digital microscopy technologies by utilizing whole slide scanning systems and virtual slides for didactic purposes, and, in combination with digital image analysis tools, for quantitative assessments of tau and amyloid burdens. 4) The NP Core will continue to participate in local and national research efforts by providing brain bank tissue materials, data from diagnostic evaluations and technical expertise. The NP core will closely collaborate with other PITT-ADRC cores and projects in joint research studies and will engage in NP Core-driven research projects. Most of these studies will focus on one of the central themes of our ADRC correlating postmortem neuropathology data with pre- mortem and post-mortem imaging data, genotype information, presence of psychosis, and neuroinflammation. 5) Brain bank cases will be utilized to educate neuropathology fellows, residents, medical students and investigators about the neuropathologic features of neurodegenerative diseases. The PITT-ADRC NP Core is committed to participate in multi-institutional collaborative research studies by providing neuropathology data and tissue resources, to continue its efforts to improve our understanding of neuropathologic correlates of psychosis in AD and PET imaging findings and to expand our knowledge of neuroinflammatory and neuropathologic phenotypes of AD risk genes.